Living donor liver transplantation (LDLT) has been widely accepted for the transplantation of children with excellent results in the recipient, and a track record of donor safety that approaches renal donation. In the face of a progressive scarcity of cadaver donors, LDLT has been extended to adults and proliferated rapidly over the last 4 years. This operation requires a more extensive hepatectomy and thus an increased risk to the donor which has not been adequately quantified. The combination of uncertain donor risk and unregulated proliferation has led to cries of alarm in both the scientific literature and the lay press. The current study will provide a structured response to these concerns and an opportunity to address fascinating biological questions inherent to this procedure. Our interest in LDLT spans nearly two decades across a broad range of surgical and medical issues. The liver transplant program in our center was constituted from the outset with the expectation that LDLT would be a significant proportion of our transplants because of the enormous waiting list in New York State. Currently LDLT accounts for nearly 1/3 of adult transplants in our center; we will perform 30 this year with continued anticipated growth in the next 5 years. Our team is broadly constituted and exceptionally capable of addressing a range of issues pertaining to structured health assessment of donor outcomes, medical indications and application of LDLT as well as surgical and biological questions. We have particular strength in epidemiology, virology, and immunology, in addition to transplant hepatology and surgery. While we recognize that a broad range of surgical questions will need to be addressed, we find two issues specific to LDLT related to the central theme of regeneration of the allograft most compelling; first, the pathophysiology and possible treatment of failure of regeneration in the recipient, ie. "small-for-size syndrome", and second, the risk of early and more severe recurrence of hepatitis C in a regenerating liver graft. The central theme of regeneration pervades LDLT, and likely hinges on inflammatory injury. Our collaborative partners, Charles Rice of the New York-Presbyterian Center for the Study of Hepatitis C and Manikkan Suthanthiran in the Transplantation Medicine program position us to test our hypotheses using novel techniques for the assessment of inflammatory cytokines and viral reinfection on the cellular level.